Reducing the Bitter Taste of Pharmaceuticals Using Cell-Based Identification of Bitter-Masking Compounds

Area of Science:

• Pharmaceutical Science
• Sensory Science
• Cell Biology

Background:

• Drug palatability, particularly bitter taste, significantly impacts patient adherence and product selection.
• Existing methods for identifying bitter taste compounds have limitations in sensitivity and correlation with sensory data.
• Bitter taste perception involves the bitter receptor (TAS2R) and subsequent intracellular pH (pH_i) changes.

Purpose of the Study:

• To develop and optimize a fluorescence-based assay for identifying bitter-tasting and bitter-taste modulating pharmaceutical compounds.
• To evaluate the optimized assay's effectiveness in screening bitter-masking agents.
• To identify potent bitter-masking compounds for the antitussive drug guaifenesin.

Main Methods:

• Optimization of a pH_i-based fluorescence assay using the dye SNARF-1 AM in human gastric parietal (HGT-1) cells.
• Inhibition of bicarbonate extrusion mechanisms and use of a low-fluorescence medium to enhance assay sensitivity.
• Screening of flavonoids for bitter-masking activity against guaifenesin and verification through human sensory trials.

Main Results:

• The optimized assay demonstrated improved signal amplitude and sensitivity compared to standard SNARF-1 AM methodology.
• Flavonoids, including eriodictyol, hesperitin, and phyllodulcin, were identified as potent bitter-masking candidates for guaifenesin.
• Human sensory trials confirmed the bitter-masking efficacy of the identified compounds.

Conclusions:

• The optimized fluorescence-based assay provides a sensitive and reliable tool for identifying bitter taste modulators.
• Eriodictyol, hesperitin, and phyllodulcin show significant potential for improving the palatability of bitter drugs like guaifenesin.
• This approach facilitates the development of more patient-friendly pharmaceutical formulations.